Adhesions are fibrous bands of tissue connecting one or more organ sites within the body. Typically, adhesions are formed in connection with tissue injury. Injury to, or ischemia of, serosal tissue results in an increased immune response at the site, with a subsequent release of serosanguinous exudate resulting in fibrin deposition at the injured site. Adhesions form as a result of the induced inflammatory response in combination with an impaired ability to lyse such fibrin deposits.
Normal tissue surfaces produce tissue plasminogen activator (t-PA) which converts inactive plasminogen to plasmin. In normal tissue, the localized proteolytic activity of plasmin dissolves fibrin deposits and thus prevents adhesion formation. However, ischemic injury to serosal surfaces retards t-PA production. Reduced t-PA production results in excessive fibrin accumulation at the injured site. Such fibrin deposits serve as a matrix for fibroblastic infiltration and proliferation. Eventually, collagenous bands form at the site of the fibrin deposit. The collagenous bands contract as healing proceeds and thereby limit movement of the affected organ or organs.
Consequently, adhesions impair movement and can obstruct proper organ function. Such mechanical impairment is responsible for a majority of chest, back, abdominal, and pelvic pain experienced by patients recovering from thoracic, abdominal, lumbar and/or gynecological surgeries. Additionally, adhesions may complicate proper healing of the surgical site and lead to loss of function, infertility, bowel obstruction and even morbidity.
Two different strategies have been employed to prevent the formation of fibrous adhesions following surgery. A first strategy includes the use of barrier materials such as oxidized cellulose membranes, polytetrafluoroethylene, or hyaluronic acid. These barrier materials are typically applied as films or sheets and sutured in place to prevent the deposition of fibrin on the injured tissue.
However, oxidized cellulose membranes, such as the Interceed.TM. Barrier are difficult to place and require a nonbleeding site. Films such as Gore-Tex.TM. have to be sutured in place. Other membranes, such as Seprafilm.TM. hyaluronic acid films, are brittle and frequently crack during application. Because a cracked film does not isolate the injured tissue from surrounding tissue, adhesion formation is not satisfactorily prevented. Such films also stick to moist gloves, other tissues and instruments thus interfering with their application. Additionally, once such films are applied to a tissue, the positioning of the film cannot be altered. Therefore, medical personnel do not have an opportunity to optimize the positioning of the film once it is applied to a tissue defect. Finally, many films, such as Gore-Tex.TM., are not biodegradable and must eventually be removed. The removal process may cause additional trauma or injury to the tissue.
Other barrier materials include viscous liquids, such as hyaluronic acid solutions, which are applied to a surgical site. However, the viscous liquid frequently does not coat the surgical site for a sufficient duration to provide the necessary barrier properties. Aqueous solutions of poloxamers, such as pluronics, which are liquids at or below room temperature, but form gels at body temperature have been developed for preventing surgical adhesions.
Although a number of these barrier materials have been approved for use in humans by the FDA, their widespread use has been limited because of their difficulty in placement and their perceived efficacy.
A second strategy for preventing adhesion formation involves the use of pharmacological agents. Typical pharmacological agents include corticosteroids and nonsteroidal anti-inflammatory agents (to inhibit fibroblastic proliferation); heparin and sodium citrate (to prevent fibrin deposition); and pentoxifylline, rt-PA, urokinase and streptokinase (to promote fibrinolysis). Unfortunately, the success of pharmacological agents in preventing adhesion formation has been limited, due to the difficulty of directing the drugs to the injury with systemic administration.
It would therefore be desirable to have a system for preventing adhesion formation which is more "user friendly" and more effective than the existing barrier materials. In particular, a barrier material that does not stick to instruments during application and is adjustable after initial application would be desirable. Additionally, a system for local administration of pharmacological agents which prevent adhesion formation would be desirable.